Publications

Gastroenterologists are at increased risk for developing recurrent thumb, hand, and elbow pain due to colonoscopy procedures. We evaluated forearm muscle loads and wrist postures during routine colonoscopy (N=12 gastroenterologists) to understand distal upper extremity musculoskeletal risk factors associated with the 4 different subtasks of colonoscopy. Bilateral forearm extensor carpiradialis (ECR) and flexor digitorum superficialis (FDS) surface electromyography and bilateral wrist postures were recorded continuously. The mean duration of colonoscopy was 24.2 (± 12.1) minutes and was dominated by the withdrawal subtask [13.7 (± 8.8) min] followed by right colon insertion [5.8 (± 4.8) min], left colon insertion [3.5 (± 3.1) min], and retroflexion [1.2 (± 2.1) min]. Median (APDF50) and peak (APDF90) left forearm muscle activity was significantly greater than right forearm muscle activity across all subtasks. Median and peak ECR muscle activity was significantly greater during the left and right colon insertion subtasks compared to retroflexion. Both wrists were predominantly in wrist extension during all phases of colonoscopy. The left forearm muscle activity was higher than right forearm activity due to differences in wrist posture and grip force. The risk factors for the left hand may be reduced with alternative designs and support mechanisms for the colonoscope head.

BACKGROUND

Sudden cardiac death (SCD) remains a major public health problem; however, its true burden remains unknown with widely variable estimates of its incidence. We aimed to examine the contemporary epidemiology and autopsy characteristics of SCD in an ethnically diverse community.

METHODS

Three physicians reviewed all deaths of individuals aged ≥20 years reported to the San Francisco medical examiner in 2007 for presentations fitting World Health Organization (WHO) SCD criteria-within 1 hour of symptom onset (witnessed) or within 24 hours of being observed alive and symptom free (unwitnessed). After comprehensive review of medical examiner investigation, WHO SCDs were classified as sudden arrhythmic death (SAD) or nonarrhythmic death. Coronary artery disease (CAD) and cardiac mass were evaluated in all SADs undergoing autopsy and compared with demographically similar accidental trauma control deaths.

RESULTS

We identified 252 WHO SCDs; 145 were SADs. Men had a 2.2-fold higher SAD rate (P < .0005). Blacks had a 3.15-fold higher SAD rate compared with whites (P = .003). Significant CAD was present in 38.9% of SADs and associated with higher SAD risk compared with control deaths (OR 2.58, 95% CI 1.12-5.97, P = .026). Mean cardiac mass was linearly associated with risk for SAD in cases without significant CAD (OR 2.06 per 100 g, 95% CI 1.43-2.98, P < .0005).

CONCLUSIONS

In a diverse, urban population, SAD incidence varied substantially by gender and race. Significant CAD accounted for far fewer SADs than previous studies but remained associated with a 2.6-fold higher risk as compared with control deaths. These findings may reflect the evolving contemporary epidemiology of SCD.

RATIONALE

Sepsis and acute lung injury (ALI) have devastatingly high mortality rates. Both are associated with increased vascular leak, a process regulated by complex molecular mechanisms.

OBJECTIVES

We hypothesized that integrin αvβ3 could be an important determinant of vascular leak and endothelial permeability in sepsis and ALI.

METHODS

β3 subunit knockout mice were tested for lung vascular leak after endotracheal LPS, and systemic vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. Possible contributory effects of β3 deficiency in platelets and other hematopoietic cells were excluded by bone marrow reconstitution experiments. Endothelial cells treated with αvβ3 antibodies were evaluated for sphingosine-1 phosphate (S1P)–mediated alterations in barrier function, cytoskeletal arrangement, and integrin localization.

MEASUREMENTS AND MAIN RESULTS

β3 knockout mice had increased vascular leak and pulmonary edema formation after endotracheal LPS, and increased vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. In endothelial cells, αvβ3 antibodies inhibited barrier-enhancing and cortical actin responses to S1P. Furthermore, S1P induced translocation of αvβ3 from discrete focal adhesions to cortically distributed sites through Gi- and Rac1-mediated pathways. Cortical αvβ3 localization after S1P was decreased by αvβ3 antibodies, suggesting that ligation of the αvβ3 with its extracellular matrix ligands is required to stabilize cortical αvβ3 focal adhesions.

CONCLUSIONS

Our studies identify a novel mechanism by which αvβ3 mitigates increased vascular leak, a pathophysiologic function central to sepsis and ALI. These studies suggest that drugs designed to block αvβ3 may have the unexpected side effect of intensifying sepsis- and ALI-associated vascular endothelial leak.